A systemic route for drug loading to lymphatic phagocytes

Lymph nodes are primary germination and proliferation sites for many types of pathogens. Maintaining therapeutic levels of appropriate chemotherapeutic agents in the lymph node tissue is critical for the treatment of both infection and cancer. This study was intended to develop a systemic route for loading lymph node phagocytes with drugs, using a lymph node specific nanocarrier. The latter is assembled as a 10-15 nm particle with a drug-carrying core and a phagocyte-homing poly(1-->6)-alpha-d-glucose based interface. Biokinetics and microdistribution of the model carrier were investigated in vivo. Nanocarrier accumulation in lymph nodes reached 30-35% dose/g in central lymph nodes, with deposition in various phagocytic cell populations. The latter included cells harboring inhaled microparticles translocated to lymph nodes from the lungs. In view of the nanocarrier ability to transport and release significant amounts of various drug substances, the data suggests feasibility of systemic drug loading to lymphatic phagocytes and, through drug release, to the neighboring cells.     

Concentration Dependent Effect of (−)‐Epicatechin on Na+/K+‐ATPase and Ca2+‐ATPase Inhibition Induced by Free Radicals in Hypertensive Patients: Comparison with L‐ascorbic Acid

Although the antioxidant properties of flavonoids are well documented, it is still unclear whether these effects are dependent on radical scavenging or iron chelating activities. Oxidative stress, a state of excessive reactive oxygen species (ROS) activity, is associated with vascular disease conditions such as hypertension. Both the anti‐ and pro‐oxidant effects of tea catechins have been implicated in the alterations of cellular functions that determine their chemoprotective and therapeutic potentials in health and diseases. The present study examined the concentration dependent (10^?7 to 10^?4 m ) effects of (?)‐epicatechin and L‐ascorbic acid on Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase activity in hypertensive patients and normal subjects. L‐ascorbic acid has been used as a positive control to compare the effect of (?)‐epicatechin. A significant (p < 0.0001) decrease in the activities of Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase was observed in hypertensive patients compared with normal subjects. We report that (?)‐epicatechin shows a significant (p < 0.001) dose‐dependent protective effect against oxidative stress induced by tert‐butyl hydroperoxide (t‐BHP), which is manisfested as a decrease in the activity of erythrocyte Na⁺/K⁺‐ATPase and Ca²⁺‐ATPase, in hypertensive patients as well as normal subjects. The effect of L‐ascorbic acid was also significant (p < 0.001) and was comparable with that of (?)‐epicatechin. Copyright © 2012 John Wiley & Sons, Ltd.     

Drug-prescribing patterns during pregnancy in the tertiary care hospitals of Pakistan: a cross sectional study

Background

Low birth weight (LBW) is considered as a major multifaceted public health concern. Seventy-two percent of LBW infants are born in Asia. An estimation of 8% LBW infants has been reported for Eastern Mediterranean region including Iran. This study investigated contributory factors of LBW in singleton term births in Tehran, Iran. Tehran is a multicultural metropolitan area and a sample from the general population in Tehran could be regarded as a representative sample of urban population in Iran.

Methods

This was a retrospective study using data from 15 university maternity hospitals in Tehran, Iran. Data on all singleton term births in these hospitals were extracted from case records during a one calendar year. Study variables included: maternal age, maternal educational level, history of LBW deliveries, history of preterm labor, cigarette smoking during pregnancy, number of parities, chronic diseases and residential area (Tehran versus suburbs of Tehran). In order to examine the relationship between LBW and demographic and reproductive variables the adjusted logistic regression analysis was performed.

Results

In all, data for 3734 term pregnancies were extracted. The mean age of women was 25.7 (SD = 5.3) years and 5.2% of term births were LBW. In addition to association between LBW and maternal age, significant risk factors for LBW were: history of LBW deliveries [adjusted odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.06–6.03], smoking during pregnancy (OR = 4.64, 95% CI = 1.97–10.95) and chronic diseases (OR for hypertension = 3.70, 95% CI = 2.25–6.06, OR for others = 2.04, 95% CI = 1.09–3.83).

Conclusion

The findings indicate that in addition to maternal age, history of LBW deliveries; smoking during pregnancy and chronic diseases are significant determinants of LBW in this population. This is consistent with national and international findings indicating that maternal variables and risk behaviors during pregnancy play important roles on LBW.     

槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分（英文）

目的：研究槟榔子（Areca catechu）粗提取物中所含的抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分及其作用机制。方法：使用70%甲醇水溶液对槟榔子进行粗提取。使用生物发光血小板凝集仪在富血小板血浆中测定槟榔子粗提取物的抗血小板聚集作用,使用分光光度计在试管内测定槟榔子粗提取物对乙酰胆碱酯酶活性的抑制作用。检测槟榔子中的多种化合物以测定槟榔子中抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分。结果：槟榔子粗提取物能够抑制花生四烯酸、二磷酸腺苷、血小板活化因子、肾上腺素及钙离子载体引起的血小板聚集,尤其对二磷酸腺苷及钙离子载体引起的血小板聚集的抑制最为明显;槟榔子粗提取物能够显著抑制乙酰胆碱酯酶的活性。在所检测的槟榔子所含化合物中,只有儿茶素对肾上腺素引起的血小板聚集有显著的抑制作用,而这种抑制作用显著弱于槟榔子粗提取物,提示槟榔子中的其他成分参与了这种抑制作用;鞣酸、没食子酸、薯蓣皂苷元和异去甲槟榔次碱能够抑制乙酰胆碱酯酶的活性,其中鞣酸的抑制作用强于槟榔子粗提取物。结论：槟榔子中含有抗血小板聚集及抑制乙酰胆碱酯酶活性的有效成分,而发挥这些功效的确切成分有待进一步的研究证实。     

Prevalence and correlates of COVID-19 vaccine hesitancy among the elderly in Qatar: A cross-sectional study

Older individuals are more vulnerable to severe coronavirus disease 2019 and medical complications. Vaccination stands as an efficient and safe vanguard against infection. However, negative attitudes and perceptions pertaining to available vaccines might hinder community inoculation. The aim of this study was to assess vaccine hesitancy and its psychosocial determinants among the elderly in Qatar.We conducted a cross-sectional study between October 15 and November 15, 2020, using a composite online survey including the Vaccine Attitudes Examination Scale in addition to questions on sociodemographic correlates and the role of healthcare professionals.The vaccine hesitancy rate was 19.5%. The main reasons for willingness to vaccinate included understanding the nature of disease and role of vaccination, in addition to information provided by physicians. Fears mainly centered around vaccine safety. Vaccine hesitators were more likely to be non-Qatari and having received the influenza vaccine at least once. Gender, marital status, socioeconomic status, educational level, and having completed childhood vaccinations were not associated with vaccine hesitancy.Efforts should be directed toward raising awareness of vaccine efficacy and safety profiles. Physicians should additionally be educated about their pivotal role in advocating vaccine acceptance. We recommend reassessing vaccine hesitancy and its associated factors following a year of campaigning and vaccine administration to identify and target vulnerable groups.     

马来西亚预防控制脊髓灰质炎免疫策略的经济学评估:注射用脊髓灰质炎灭活疫苗与口服脊髓灰质炎减毒活疫苗

1背景由马来西亚卫生部和马来西亚国民大学(UKM)联合承担的研究项目,主要研究者是Dr·Syed Mohamed AI Junid,研究中心是吉隆坡总医院(GHKL)儿童研究所、UKM医院儿科病房及乌鲁冷岳区(Hulu Langat)医疗中心,研究时间自2004年1月~2006年6月。研究开始前分别获得了马来西亚卫生部     

Current trends in imaging evaluation of acute cholecystitis

This study was designed to retrospectively determine recent clinical trends of initial radiological evaluation in patients pathologically proven to have acute cholecystitis (AC) and to assess the methodology that led to its diagnosis. Over a 28-month period, the medical records and imaging studies of 117 consecutive patients who had pathologically confirmed AC were retrospectively analyzed. The sensitivities of ultrasound (US) and hepatobiliary ^99mTc-iminodiacetic acid (HIDA) were computed. The false-negative scans were retrospectively reviewed by a blinded radiologist to determine the limitations and advantages of each modality. The 117 patients were grouped into six categories based on the type of imaging examination they underwent prior to cholecystectomy: initial US evaluation only (n=80, 68.4%), initial US followed by HIDA (n=17, 14.5%), initial HIDA only (n=2, 1.7%), initial HIDA followed by US (n=3, 2.6%), initial CT (n=5, 4.3%), and no imaging evaluation (n=10, 8.6%). HIDA scan had a calculated sensitivity of 90.9% (20 true-positive, 2 false-negative) while US had a sensitivity of 62% (62 true-positive, 38 false-negative). Current practice in the initial radiological evaluation of acute cholecystitis remains outdated. The vast majority of patients in our study group were initially worked up using US, although HIDA scan has been shown to have greater sensitivity for the diagnosis of acute cholecystitis.     

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism